Respiratory syncytial virus (RSV) is the most important cause of serious lower respiratory tract disease in infants and young children worldwide, and is also a threat to elderly and immune compromised patients. In the United States, RSV infections result in up to 126,000 infant hospitalizations and up to 60,000 elderly adult hospitalizations per year. Since natural RSV infection does not induce durable long-term immunity, patients are susceptible to re-infection with the same and different strains of virus throughout life. RSV is associated with secondary infections such as otitis media, and it may predispose young children for asthma-related illness later in life.
After more than 40 years of effort, there is no safe and effective RSV vaccine. The earliest attempts to develop a formalin-inactivated alum-precipitated RSV (FI-RSV) vaccine in the 1960's actually appeared to predispose vaccinated children to more severe disease and even death upon subsequent natural infection. The exact mechanism of this response has not been fully characterized, but it appears to be dependent on a skewing of the immune response toward an inflammatory Th2-dominant phenotype characterized by inappropriate activation of cytokine and chemokine pathways.
Given the economic impact of RSV disease, estimated at nearly $700 million per year in the US in 2004, and the life-threatening complications that can result from RSV infection in infants, elderly, and immunocompromised patients, development of safe and effective RSV vaccines is a high priority.
There is a need for improved antigenic compositions suitable for stimulating an immune response to RSV.